Este trabalho consiste no estudo teórico e experimental das emendas dentadas em madeira laminada colada (MLC), cujo objetivo principal é avaliar o método proposto no Projeto da Nova Norma Brasileira PNBR 7190 (1996) para a caracterização da MLC, com ênfase às emendas dentadas. As espécies de madeira estudadas foram o Pinus elliottii e o Eucalipto grandis e o adesivo utilizado foi o CASCOPHEN RS-216, à base de resorcinol, produzido pela Alba Química Indústria e Comércio Ltda. A emenda dentada usada no estudo foi a correspondente ao comprimento de 20 mm da DIN 68140, geometria esta adotada pelo parque produtor de MLC no país. Nos ensaios são avaliadas as resistências ao cisalhamento na lâmina de cola, a tração normal à lâmina de cola e a resistência a tração das emendas dentadas. O desempenho das ligações foi avaliado em função da relação entre os valores obtidos nos ensaios com madeira colada e madeira maciça, bem como pelo modo de ruptura dos mesmos. Como conclusão obteve-se que o processo de colagem adotado foi bem sucedido para todos as amostras de caracterização da MLC, independente da espécie de madeira e do tipo de ruptura obtido. O método proposto no Projeto da Nova Norma Brasileira PNBR 7190 (1996) mostrou-se adequado para a caracterização das propriedades de resistência da MLC. / This work consist in the theoretical and experimental study of finger joints in glued laminated timber (GLULAM), with main objective to evaluate the method proposed in the New Brazilian Draft Code PNBR 7190 (1996) to characterization of GLULAM, with emphasis to finger joints. The species of wood studied were the Pinus elliottii and Eucalipto grandis and the adhesive was the CASCOPHEN RS-216, resorcinol-based, produced by Alba Química Indústria e Comércio Ltda. The geometry of finger joint used in the study was the correspondent to DIN 68140, this is the adopted by producer park of GLULAM in the country. In the tests were evaluated the shear resistance of glue lamina, the perpendicular tension resistance of glue lamina and parallel to grain tension resistance of finger joints. The performance of jointing was evaluated as a function of the relation between the values obtained in the tests with glued wood and clear wood, as well as rupture mode. Concluding remarks that gluing process adopted was well successful to all specimens of wood specie and rupture mode. The method proposed by New Brazilian Draft Code PNBR 7190 (1996) is adequate to characterization of the resistance properties of GLULAM.

by Cecilia Li Tsang Wai Ping. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1993. / Includes bibliographical references (leaves [175-185]). / ABSTRACT / AKNOWLEDGEMENTS / Chapter CHAPTER ONE --- INTRODUCTION / Chapter 1.1 --- INTRODUCTION --- p.1 / Chapter 1.2 --- AIMS OF STUDY --- p.3 / Chapter CHAPTER TWO --- RHEUMATOID ARTHRITIS / Chapter 2.1 --- DEFINITION --- p.4 / Chapter 2.2 --- PREVALENCE --- p.4 / Chapter 2.3 --- AETIOLOGY --- p.4 / Chapter 2.4 --- PATHOLOGY --- p.5 / Chapter 2.5 --- CLINICAL FEATURES OF RHEUMATOID ARTHRITIS IN HAND --- p.5 / Chapter 2.6 --- CRITERIA FOR DIAGNOSIS OF RHEUMATOID ARTHRITIS --- p.7 / Chapter CHAPTER THREE --- HAND DEFORMITIES IN RHEUMATOID ARTHRITIS / Chapter 3.1 --- THE HAND --- p.9 / Chapter 3.2 --- THE RHEUMATOID HAND --- p.13 / Chapter 3.4 --- CAUSES OF FLEXION CONTRACTURE AT THE PROXIMAL INTERPHALANEAL JOINT --- p.16 / Chapter CHAPTER FOUR --- SPLINTING FOR THE RHEUMATOID HAND / Chapter 4.1 --- SPLINTING IN RHEUMATOID ARTHRITIS --- p.19 / Chapter 4.2 --- SPLINTING FLEXION CONTRACTURES AT THE PROXIMAL INTERPHALANGEAL (PIP) JOINTS --- p.24 / Chapter 4.3 --- THE MECHANICAL ANALYSIS OF SPLINT DESIGN --- p.32 / Chapter CHAPTER FIVE --- HAND ASSESSMENT IN RHEUMATOID ARTHRITIS / Chapter 5.1 --- INTRODUCTION --- p.41 / Chapter 5.2 --- A REVIEW OF THE STANDARDISED HAND FUNCTION ASSESSMENT --- p.42 / Chapter 5.3 --- MEASUREMENT OF GRIP STRENGTHS --- p.48 / Chapter 5.4 --- MEASUREMENT OF ACTIVE RANGE OF MOTION OF FINGER JOINTS --- p.52 / Chapter CHAPTER SIX --- DEVELOPMENT OF HAND EVALUATION SYSTEM in RHEUMATOID ARTHRITIS / Chapter 6.1 --- INTRODUCTION --- p.56 / Chapter 6.2 --- AIMS OF STUDY --- p.56 / Chapter 6.3 --- DEVELOPMENT OF THE HAND EVALUATION SYSTEM --- p.57 / Chapter 6.4 --- A COMPARATIVE STUDY OF HAND GRIP ASSESSMENT TOOLS: THE JAMAR DYNAMOMETER AND THE REC PROTOTYPE GRIP ANALYSER --- p.58 / Chapter 6.5 --- A COMPARATIVE STUDY ON THE JEBSEN HAND FUNCTION TEST IN HONG KONG --- p.67 / Chapter 6.6 --- ASSESSMENT OF FUNCTIONAL RANGE OF MOTION --- p.77 / Chapter 6.7 --- CONCLUSION --- p.83 / Chapter CHAPTER SEVEN --- THE MAIN STUDY / Chapter 7.1 --- INTRODUCTION --- p.85 / Chapter 7.2 --- RESEARCH DESIGN --- p.85 / Chapter 7.3 --- DEFINITION OF VARIABLES --- p.86 / Chapter 7.4 --- SUBJECT SELECTION --- p.89 / Chapter 7.5 --- EXPERIMENTAL PROCEDURES --- p.89 / Chapter 7.6 --- PILOT STUDY --- p.91 / Chapter 7.7 --- STATISTICAL ANALYSIS OF DATA --- p.94 / Chapter CHAPTER EIGHT --- RESULTS / Chapter 8.1 --- RESULTS --- p.95 / Chapter 8.1.1 --- Age distribution --- p.96 / Chapter 8.1.2 --- Occupation --- p.98 / Chapter 8.1.3 --- Functional class --- p.98 / Chapter 8.1.4 --- Group characteristics --- p.99 / Chapter 8.1.5 --- Comparison of the effect of corrective splints on hand functions of clients --- p.100 / Chapter 8.1.6 --- Comparison of the effect of two types of corrective splintage on hand functions of clients --- p.103 / Chapter 8.2 --- SUMMARY --- p.113 / Chapter 8.2.1 --- Summary of findings --- p.113 / Chapter 8.2.2 --- Compliance and complication of the splint intervention programme --- p.114 / Chapter CHAPTER NINE --- DISCUSSION / Chapter 9.1 --- INTRODUCTION --- p.116 / Chapter 9.2 --- COMMENTS ON THE HAND EVALUATION PROTOCOL … --- p.117 / Chapter 9.3 --- DISCUSSIONS OF THE RESULTS OF THE PILOT STUDY --- p.121 / Chapter 9.4 --- DISCUSSION OF THE RESULTS OF THE MAIN STUDY --- p.125 / Chapter 9.5 --- IMPLICATION OF STUDY INTO OCCUPATIONAL THERAPY PRACTICE --- p.130 / Chapter 9.6 --- LIMITATION OF THE STUDY --- p.131 / Chapter 9.7 --- SUMMARY --- p.132 / Chapter CHAPTER TEN --- CONCLUSION AND RECOMMENDATIONS / Chapter 10.1 --- CONCLUSION --- p.134 / Chapter 10.2 --- RECOMMENDATIONS --- p.138 / Chapter 10.3 --- SUGGESTIONS FOR FURTHER RESEARCH --- p.139 / APPENDICES / REFERENCES

Made available in DSpace on 2014-06-11T19:22:18Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-02-28Bitstream added on 2014-06-13T20:09:06Z : No. of bitstreams: 1 oliveira_mws_me_sjrp.pdf: 3828836 bytes, checksum: 680508c509760317dd7d5d894a6d7f85 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / O objetivo deste trabalho é abordar o campo de orientação de impressões digitais, técnicas para sua extração e algumas de suas aplicações na área de processamento de imagens de impressões digitais. Almejando diminuir a interferência humana no processo de regularização do campo de oreintação foi, também, proposto um método para detecção da área da impressão digital, de forma automática no caso de imagens com boa qualidade e semi-automática no caso de imagens latentes, baseado em contronos ativos. Os testes realizadoscomprovam a eficácia das técnicas propostas / The aim of this study is to discuss the orientation field of fingerprints, techniques for extraction and some of its applications in fingerprint image processing. Aiming to reduce human interference in the process of regularization of the orientation field was also proposed a method for fingerprint area detection, automatic in the case of good quality images and semi-automatic in the case of latent images, which was based on active contours. The computational tests showed the effectiveness of proposed techniques

O objetivo deste trabalho é o estudo da resistência e rigidez das emendas dentadas à fadiga na tração com as finalidades de propor uma metodologia de ensaio e estimar um coeficiente redução da resistência à fadiga na tração das emendas dentadas em relação a madeira maciça, contribuindo para a caracterização destas ligações. Foram utilizadas duas espécies de madeira, Pinus caribea hondurensis e Eucalyptus grandis, e dois tipos de adesivos sendo um industrial à base de fenol-resorcinol e um poliuretano à base de resina de mamona desenvolvido no Instituto de Química de São Carlos. Foram realizados ensaios cíclicos para três níveis de freqüência (1 Hz, 5 Hz e 9 Hz) e três níveis de tensão (90%, 75% e 60% da resistência) a uma relação R = 0,1. Com base nos resultados foram propostos coeficientes de redução de resistência à fadiga da emenda dentada em relação à madeira maciça e verificar que não há variação significativa da rigidez em função do número de ciclos. / The aims of this work is the study of the fatigue strength and stiffness of the finger joints in tension, in order to propose an experimental methodology and to determine a strength reduction coefficient, in relation to solid wood, contributing to the characterization of these joints. Two wood species, Pinus caribea hondurensis and Eucalyptus grandis, and two adhesives types were used, being an industrial one phenol-resorcinol based and a poliuretane castor oil resin based, developed at the lnstitute of Chemistry of São Carlos. Cyclical tests were accomplished in three frequency levels (1 Hz, 5 Hz and 9 Hz) and three tension levels (90%, 75% and 60% of the strength) to a relationship R = 0,1. Based on the results, it were proposed strength reduction coefficients in relation to solid wood, for finger joints under fatigue in tension, and to concluded that there is no significant variation in stiffness with the cycle numbers.

Este trabalho consiste no estudo teórico e experimental das emendas dentadas em madeira laminada colada (MLC), cujo objetivo principal é avaliar o método proposto no Projeto da Nova Norma Brasileira PNBR 7190 (1996) para a caracterização da MLC, com ênfase às emendas dentadas. As espécies de madeira estudadas foram o Pinus elliottii e o Eucalipto grandis e o adesivo utilizado foi o CASCOPHEN RS-216, à base de resorcinol, produzido pela Alba Química Indústria e Comércio Ltda. A emenda dentada usada no estudo foi a correspondente ao comprimento de 20 mm da DIN 68140, geometria esta adotada pelo parque produtor de MLC no país. Nos ensaios são avaliadas as resistências ao cisalhamento na lâmina de cola, a tração normal à lâmina de cola e a resistência a tração das emendas dentadas. O desempenho das ligações foi avaliado em função da relação entre os valores obtidos nos ensaios com madeira colada e madeira maciça, bem como pelo modo de ruptura dos mesmos. Como conclusão obteve-se que o processo de colagem adotado foi bem sucedido para todos as amostras de caracterização da MLC, independente da espécie de madeira e do tipo de ruptura obtido. O método proposto no Projeto da Nova Norma Brasileira PNBR 7190 (1996) mostrou-se adequado para a caracterização das propriedades de resistência da MLC. / This work consist in the theoretical and experimental study of finger joints in glued laminated timber (GLULAM), with main objective to evaluate the method proposed in the New Brazilian Draft Code PNBR 7190 (1996) to characterization of GLULAM, with emphasis to finger joints. The species of wood studied were the Pinus elliottii and Eucalipto grandis and the adhesive was the CASCOPHEN RS-216, resorcinol-based, produced by Alba Química Indústria e Comércio Ltda. The geometry of finger joint used in the study was the correspondent to DIN 68140, this is the adopted by producer park of GLULAM in the country. In the tests were evaluated the shear resistance of glue lamina, the perpendicular tension resistance of glue lamina and parallel to grain tension resistance of finger joints. The performance of jointing was evaluated as a function of the relation between the values obtained in the tests with glued wood and clear wood, as well as rupture mode. Concluding remarks that gluing process adopted was well successful to all specimens of wood specie and rupture mode. The method proposed by New Brazilian Draft Code PNBR 7190 (1996) is adequate to characterization of the resistance properties of GLULAM.

Suppressor of Hairy-wing [Su(Hw)] is a twelve zinc-finger (ZF), DNA binding transcription factor. Su(Hw) has been well characterized as critical component of the gypsy insulator complex, required for the enhancer blocking and the barrier activity of the insulator. In addition to gypsy, Su(Hw) localizes to ~3,000 binding sites in the Drosophila genome, with association to a subset of sites required for female germline development. Loss of Su(Hw) results in activation of a developmental checkpoint and apoptosis at mid- oogenesis, with a critical role during oogenesis in down-regulation of neural genes. Studies of Su(Hw) function have identified transcriptional activator, repressor and insulator roles at distinct binding sites. Current investigations aim to understand the factors that dictate the regulatory output of Su(Hw) at individual sites in the Drosophila genome, with a focus on the ZF domain. A genetic screen was completed to generate novel mutations in su(Hw). After screening more than 8,000 mutagenized chromosomes, we identified four new su(Hw) alleles, including two deletion mutations and two amino acid substitutions disrupting individual ZFs (ZF4 and ZF8). Studies of the ZF4 mutant, Su(Hw)M4M393, revealed that Su(Hw) requires this ZF for female fertility, but notgypsy insulator function. To achieve a comprehensive understanding of the Su(Hw) ZF domain, we generated Su(Hw) mutant proteins carrying disruptions in individual ZFs. Analyses utilizing these proteins have defined the requirement for each ZF in DNA association in vitro. To complement extant ZF alleles, Su(Hw) ZF mutants were expressed in vivo. Analyses of these mutants established how each ZF contributes to SBS occupancy, gypsy insulator function and female fertility. Gene expression and ChIP analyses suggest that some Su(Hw) ZFs may execute roles apart from direct DNA recognition. Genome-wide binding analyses of Su(Hw)M4M393, combined with previous studies, found that the SBS binding motif contains three DNA sequence cores (termed upstream, central and downstream). Analyses of these sequence cores in combination with Su(Hw) ZF mutants have outlined which ZFs associate with each core. Interestingly, the class containing all three sequence cores represents high occupancy SBSs that are enriched for protein factors from functional classes including transcriptional repression, nucleosome remodeling and DNA replication. The class containing the upstream and central core correlates with insulator function, while the class containing the central and downstream cores correlates with activation or repression of Su(Hw) target genes. Finally, in vitro studies of Su(Hw) ZF mutants revealed a DNA bound conformation distinct from wild type Su(Hw). Su(Hw) is a versatile transcription factor able to act as an insulator, activator and repressor. Analyses of SBSs with these functions suggest that DNA sequence, ZF usage, protein partnership and Su(Hw) conformation, combine to dictate regulatory output. Together, these studies provide insight into how discrete ZFs contribute to the roles of a multifunctional, polydactyl transcription factor.

The zinc finger protein, zBED6, is a transcriptional regulator of IGF2 along with hundreds of other genes relating to development and growth. Studies on the growth of commercially bred pigs discovered a single nucleotide substitution in the third intron of IGF2 which disrupts the binding of zBED6 and is responsible for the three-fold upregulation of IGF2 in skeletal muscle. The mutation is linked to decreased subcutaneous fat deposition, larger organ size, and increased skeletal muscle mass. Three different constructs of the zBED6 protein made by Björklund 2018 were expressed and purified to characterize their binding affinity, where one contained both zinc finger domains and two of the constructs contained only one zinc finger domain each. Electrophoretic mobility shift assay protocol was optimized to determine the apparent Kd (= 210 ± 31nM) for the full-length construct C13 and to determine which zinc finger domain was sensitive to the mutation in the IGF2 gene. The first zinc finger domain seems to be more specific in its binding target. Preliminary microscale thermophoresis results were highly variable, needing further optimization of the protocol in order to obtain a full binding curve. The next steps involve site directed mutagenesis of residues binding DNA to determine which interactions are the most significant and possibly crystallization studies as well.

Der Hefepilz Candida albicans gehört zu den opportunistischen Infektionserregern. Er ist Teil der natürlichen Mikroflora der Schleimhäute des Gastrointestinal- und Urogenitaltraktes des Menschen. Bei Störungen des natürlichen Gleichgewichts dieser Flora kann es zu oberflächlichen Mykosen, z. B. der oropharyngealen Candidiasis (Mundsoor), kommen. Besonders immunsupprimierte Patienten, wie AIDS-Patienten, leiden häufig unter immer wiederkehrenden Infektionen, die mitunter auch zu schwerwiegenden Infektionsverläufen, bis hin zu lebensbedrohlichen systemischen Mykosen führen können. Zur Therapie solcher Erkrankungen werden oft Ergosterolbiosyntheseinhibitoren, wie Fluconazol, eingesetzt. Besonders bei wiederkehrenden Infektionen und wiederholender Therapie ist C. albicans in der Lage, gegen diese häufig verabreichten Antimykotika Resistenzen zu entwickeln. Hierbei spielen Zink-Cluster-Transkriptionsfaktoren eine zentrale Rolle. Zink-Cluster-Proteine gehören zu einer pilzspezifischen Familie von Transkriptionsfaktoren, die ein großes Spektrum an zellulären Prozessen regulieren. Die gut charakterisierten Regulatoren Upc2, Tac1 und Mrr1 gehören zu den Zink-Cluster-Transkriptionsfaktoren, die maßgeblich zur Resistenzentwicklung von C. albicans beitragen. Upc2 kontrolliert die Expression vieler Ergosterolbiosynthesegene, besonders die von ERG11, welches für die Zielstruktur des gängigen Antimykotikums Fluconazol kodiert. Tac1 und Mrr1 hingegen regulieren die Expression von Multidrug-Effluxpumpen, den ABC-Transportern CDR1 und CDR2 bzw. dem Major Facilitator MDR1. Gain-of-function-Mutationen in diesen Transkriptionsfaktoren resultieren in einer konstitutiven Überexpression ihrer Zielgene und sind verantwortlich für die Resistenz vieler klinischer Isolate. In dieser Arbeit wurde gezeigt, dass die Fusion von Mrr1 mit der Gal4-Aktivierungsdomäne von Saccharomyces cerevisiae zu einem konstitutiv aktiven Hybridtranskriptionsfaktor führte, der eine MDR1-Überexpression bewirkte und Fluconazolresistenz vermittelte. Dieses Hybridprotein vermittelte sogar eine höhere Resistenz als ein Mrr1 mit natürlich vorkommenden gain-of-function-Mutationen. Analoge Fusionen mit Tac1 und Upc2 resultierten ebenfalls in einer konstitutiven Aktivierung dieser Transkriptionsfaktoren, die einen starken Anstieg der Fluconazolresistenz zur Folge hatte. Daraus ergab sich die Schlussfolgerung, dass dies eine generelle Methode sein könnte, die Zink-Cluster-Transkriptionsfaktoren künstlich zu aktivieren und so ihre biologischen Funktionen zu offenbaren, ohne die genauen Bedingungen für ihre Aktivität zu kennen. Deshalb wurde auf der Basis dieser Strategie eine Bibliothek von C.-albicans-Stämmen konstruiert, in der alle 82 putativen Zink-Cluster-Transkriptionsfaktoren in dieser möglicherweise hyperaktiven Form exprimiert werden. Untersuchungen dieser Bibliothek offenbarten neue Transkriptionsfaktoren, die Fluconazolresistenz vermittelten, aber auch noch unbekannte Regulatoren der Morphogenese und andere Phänotypen konnten beobachtet werden. Um einen tieferen Einblick in die Funktionsweise zu bekommen, wurden die Transkriptionsprofile der vier Transkriptionsfaktoren ermittelt, die in ihrer hyperaktiven Form die höchste Fluconazolresistenz bewirkten. Dabei stellte sich heraus, dass die zwei künstlich aktivierten (*) Regulatoren ZCF34* und ZNC1* die Expression der wichtigsten Multidrug-Effluxpumpe CDR1 stark hochregulierten. Der Transkriptionsfaktor mit dem vorläufigen Namen ZCF34 konnte im Verlauf dieser Arbeit als ein wichtiger Regulator für die CDR1-Expression identifiziert werden. Er ist sowohl an der Aktivierung der Expression von CDR1 beteiligt als auch für die basale CDR1-Promotoraktivität notwendig. Aus diesem Grund wurde er in MRR2 (multidrug resistance regulator 2) umbenannt. Mit der Entdeckung eines neuen Regulators der wichtigsten Multidrug-Effluxpumpe von C. albicans wurde ein wichtiger Beitrag zum Verständnis der Regulation solcher Transporter geleistet. Die Überexpression dieser Pumpen ist einer der häufigsten Resistenzmechanismen in C. albicans. Auf diesem Wege kann Resistenz gegen strukturell völlig unterschiedliche Antimykotika bewirkt werden. Somit stellen sowohl diese Effluxpumpen, als auch deren Regulatoren mögliche Angriffsziele für die Entwicklung neuer oder Weiterentwicklung bereits vorhandener Antimykotika dar. / The yeast Candida albicans is an oppotunistic fungal pathogen, usually a harmless colonizer of mucosal surfaces of the gastrointestinal und urogenital tract of healthy people. If the balance of this microflora is disturbed, it can cause superficial mycoses, like oropharyngeal candidiasis. Especially immunocompromised patients, like AIDS patients suffer from recurrent infections, occasionally causing life-threatening systemic infections. The antifungal agent fluconazole, which inhibits ergosterol biosynthesis, is frequently used to treat Candida-infections. Particularly during long term treatments of recurrent infections, C. albicans can develop resistance to the commonly used antifungal drugs. Zinc cluster transcription factors often play key roles in the development of such resistances. The zinc cluster proteins are a fungus-specific family of transcription factors that regulate a variety of cellular processes. The well characterized regulators Upc2, Tac1 und Mrr1 are among these zinc cluster transcription factors, being significantly involved in mediating drug resistance. Upc2 controls the expression of ergosterol biosynthesis genes, e. g. of ERG11, encoding the target enzyme of fluconazole. Tac1 and Mrr1 regulate the expression of multidrug efflux pumps, the ABC transporters CDR1 and CDR2 and the major facilitator MDR1, respectively. Gain-of-function mutations in these transcription factors result in constitutive overexpression of their target genes and are responsible for drug resistance in many clinical C. albicans strains. In this thesis it could be shown that fusion of the full-length Mrr1 with the Gal4 activation domain from Saccharomyces cerevisiae produced a constitutively active hybrid transcription factor that mediated MDR1 overexpression and increased drug resistance. The hybrid transcription factor exhibited even higher activity than Mrr1 with a naturally occurring gain-of-function mutation. Analogous fusions with Tac1 and Upc2 also resulted in constitutively activated transcription factors that conferred strongly increased drug resistance, suggesting that this might be a generally applicable approach for the artificial activation of zinc cluster transcription factors, which could reveal their biological function without prior knowledge about inducing conditions. Therfore a library of C. albicans strains expressing all 82 predicted zinc cluster transcription factors of this pathogen was constructed, by using this strategy, resulting in strains with potentially hyperactive regulators. Screening of this comprehensive set of strains revealed novel transcription factors mediating drug resistance, but also previously unknown regulators of morphogenesis and other phenotypes. To gain insight into their mechanism of action, transcriptional profiles were determined of the four transcription factors that produced the strongest increase in fluconazole resistance when expressed in a hyperactive form. This analysis revealed that two out of these four artificially activated (*) transcription factors, ZCF34* and ZNC1*, strongly upregulate the expression of the most important multidrug efflux pump CDR1, which could be verified by Northern hybridization. The transcription factor previously named ZCF34 could be identified as a new and important regulator of CDR1, being involved in the activation of CDR1 expression as well as in basal promoter activity of this pump. Therefore it was renamed MRR2 (multidrug resistance regulator 2). The identification of MRR2 as a new regulator of the most important multidrug efflux pump in C. albicans represents a major step forward in understanding the regulation of such transporters. The overexpression of these efflux pumps is one of the most common resistance mechanism in C. albicans, conferring resistance to many structurally and functionally unrelated toxic compounds. Therefore these transporters, as well as their regulators, provide potential tagets of new or further developed antifungal agents.

The interplay of structures in the finger that facilitate movement is complex and not yet fully understood. Subtle finger injuries are often missed during the initial assessment in the Emergency Department, because clinical examination of the acutely injured hand can be difficult. The consequences of unrecognized finger injuries can be devastating for the patient. Ultrasound imaging of tendons is a useful investigative tool although little has been published regarding the reliability of finger tendon measurements. The overall objective of this project was to establish if bedside ultrasound imaging of tendons was possible and useful in the setting of acute injury. The project was divided into two studies.In the first study, 65 apparently normal volunteers were scanned to allow the principal investigator to practise and refine the ultrasound technique. The dimensions of the Extensor Digitorum Longus and two flexor tendons combined (Flexor Digitorum Profundus and Flexor Digitorum Superficialis) were measured in both transverse and longitudinal sections. Fifteen of the volunteers had their left middle fingers scanned twice within 48 hours to establish the test to retest reliability of tendon measurement. The established scanning technique was simple to perform and the scans, including both static and real time images, were completed within five minutes. All volunteers were able to tolerate a full scan. Measurement of tendon width showed fair to good reliability (Intra class correlation [ICC] of flexor tendons = 0.66, ICC of extensor tendon = 0.54). However measurement of the depth of all the tendons was unreliable test to retest (ICC < 0.37).In the second study, 30 patients who presented to the Emergency Department at Lismore Base Hospital with hand injuries were scanned for evidence of tendon injury and tendon gliding restriction. The patient’s ability to tolerate ultrasound examination was investigated. The scan findings were compared with the clinical findings and then to the operation report or to the patient’s self reported outcome, one month after injury.Patients were willing to undergo ultrasound examination regardless of the extent of their injury. There was a significant difference (p = 0.04) in scan tolerance related to the site of injury with 50% of those with extensor surface injuries having completed scans in comparison to 36% with flexor surface injuries and 9.1% of finger tip injuries. Injury mechanism was not related to scan tolerance.Excluding a partial tendon laceration was technically difficult due to the presence of anisotropy artefact. However, all complete tendon lacerations were successfully identified prior to surgery. The gliding of the tendons was easy to visualize and abnormal gliding was found to be a marker of tendon injury.The overall results show that ultrasound imaging of finger tendons at the bedside in the Emergency Department is a feasible examination to perform. The addition of ultrasound examination, however, did not identify any cases of tendon injury not already suspected on routine clinical examination.Therefore, this pilot study suggests that routine use of ultrasound examination to detect finger tendon injury in the Emergency Department setting will not prove to be a useful investigation. There may be a role for ultrasound as a screening tool as the gliding of normal tendons differed noticeably from the gliding of injured tendons. The presence of normal tendon gliding may be helpful in identifying those patients that are safe to be discharged from the Emergency Department without further evaluation.

This thesis sought to: 1) examine the effect of a number of organism and task constraints on the control of two forms of physiological tremor, namely postural and finger-pinch force tremor; and 2) determine if the expected constraint-related changes in tremor output were associated with alterations in the control strategy utilised by the performer. The organism constraints were age and resistance-training (for both forms of tremor), while the task constraints were visual feedback, target size and limb preference (postural tremor) and mean force, target shape and limb preference (force tremor). The postural (index finger) tremor amplitude of young adults was significantly greater in the augmented vision (AV) than normal vision (NV) conditions and when using the non-preferred than preferred limb. Even greater differences/changes in postural tremor amplitude were observed as a function of aging and training. Older adults had significantly more index finger tremor amplitude than young adults. Regardless, the older adults who completed a six weeks program of unilateral strength- or coordination-training were able to significantly reduce their tremor amplitude. Although the training-related reductions in tremor amplitude were of a greater magnitude for the trained than untrained limb, a significant reduction in the tremor amplitude of the untrained limb was also observed for the coordination-training group. All of these significant differences/changes in tremor amplitude were associated with significant changes in a number of other dependent variables. For example, the task- and age-related increases in tremor amplitude were primarily a result of greater 8-12 Hz tremor power and were associated with increased EMG activity/co-activation of the extensor digitorum (ED) and flexor digitorum superficialis (FDS) muscles and a significant reduction in intra-limb (index finger-hand and forearm-upper arm) coupling. The significant reductions in tremor amplitude observed for the resistance-trained older adults was a result of a significant decline in 8-12 Hz power and were associated with a significant reduction in ED and FDS co-activation. However, no significant change in intra-limb coupling was observed. The overall trends observed in the results for the finger-pinch force tremor experiments were similar to those for postural tremor. Older adults had significantly more finger-pinch force tremor (i.e. force variability and targeting error) than young adults, although older adults who performed six weeks of unilateral strength-training were able to significantly reduce the force variability and targeting error of the trained limb. No significant training-related reduction in force tremor was however observed for the untrained limb. The significant age-related increase in force tremor was a result of greater low frequency (less than 2 Hz) power and was associated with a significant loss of inter-digit force sharing and coupling as well as tactile sensitivity. Interestingly, the training-related decreases in force tremor were not associated with significant changes in any of the frequency, sharing or coupling measures. Collectively, the results of the five experiments contained in this thesis add much to our understanding of postural and force tremor. Results indicated that numerous task and organism constraints can have a substantial effect on the resulting tremor output. Furthermore, the task- and age-related differences in the power spectral, muscle activity and coupling measures suggested that the changes in tremor output were the result of the use of an altered (sub-optimal) control strategy. The age-related increase in postural and force tremor amplitude may therefore reflect not only an overall decline in neuromuscular system function, but also the relative inability of older adults to effectively coordinate the output of numerous degrees of freedom (limb segments). The effect of the aging process on tremor output was somewhat reversible, with the older adults who performed resistance-training significantly improving their control of both postural and force tremor. There was some evidence that resistance-training could produce cross-education effects in older adults, although these were only statistically significant for postural tremor amplitude in the coordination-training group and for wrist flexion strength in the strength-training group. The relative brevity of the training program (6 weeks) and the observable cross-education effects suggest that the reduction in tremor amplitude and increases in strength were primarily a result of neural adaptations. Such findings further support the prescription of resistance-training for improving physical function in older individuals.